Steroid alpha-halo ketals



`atoms of the pregnane skeleton such as, for example,.ini

. chloro-1laeacetoxy-17a-hydroxypregnane-3,20-dione 3,20- a diketals, Y4-.chloro-12,hydroxypregnane 3,20 ,-.dione 3,20- 'cliketals,` 4chlorol2 acetoxypregnane-3,20 dione 3,20-

. diketals, 4-c`hloro 11-pregnene-3,20 dione 3,20-diketals, l

- ,i-chloro4 9(11)pregnene 3,20 dione 3,20 diketals, 4-

;chloro-6-hydroxypregnane-3,20 dione 3,20 diketals, 4- .chloro-6-acetoxypregnane, 3,20-dione 3,20 diketals, .the :corresponding 4-bromo compounds, and the like.

The starting steroid 4-halo-3,20diketal compound for the methodof the presentV invention are prepared by reacting a steroid 4-halo-3,20diketone having a pregnane -carbon skeleton with an alk'ane-LZ-diol or an alkane 1,3

:diol in the presence of an acid catalyst at a temperature be- `low about 200 degrees centigrade, preferably under reux conditions, to cause conversion of the 3- and ZO-ketone groups to ketal groups. .In carrying out the reaction the 4-halo-3,20diketone compound is admixed with at least -the theoretical amount of the alkane1,2diol or alkane- 1,3-dio1 in an organic solvent and at a temperature between about twenty and about 200 degrees centigrade, preferably between about twenty `and about 150 degrees centigrade. Ordinarily, it is preferred' to use an excess of the alkane- .diol,V preferably between about ve and about fifty moles .per mole of the steroid. The time required for reaction i Y is not critical and may be varied between about one and about 24 hours, the length of time being-somewhat dependent on the temperature, the ketalizing reagent and vcatalyst employed, as will be apparent to one skilled in Vthe art. i. l The ketalizing reaction can be conducted in any organic solvent .with whichV the reactants and products are nonreactive,Y such as,'for example, benzene, toluene, xylene, methylene chloride, petroleum ether, ether, or the like. However, the preferred solvents are those which form an -azeotrope with water and hence remove the water as it is 'formed in the c ourse of the reaction. lFor this reason the `reaction Vislusually vconducted at the reflux temperature` of ',the mixture, Vsuch temperature depending, of

course, upon the'f'solvent and the 'ditions, cfg., pressure, employed;-V .-The-,ketal-forming agents which may be employed in Vthepreparation of the starting diketal compoundsA are particular reaction con- L talkane-LZ-diols and alkane1,3diols such as, for example, v

ethylene glycol, propane-1,2-diol, propane-1,3-diol,kv butane-,1,2-diol, -pentane-LZ-diol, S-methylpentane-1,2-diol, hexane-l-diol, octane-1,2-diol,v andthe like. The catdiketaln the presence of an organic solvent which is non-reactive under the conditions of reaction. Reducing agents such as, for example, lithium aluminum hydride, lithium borohydride, sodium borohydride, hydrogen in the presence of catalysts such as platinum or Raney nickel, and others are operative, with lithium aluminum hydride being preferred. Solvents such as, for example, ether, benzene, tetrahydrofuran, petroleum ether andothers are satisfactory. In the preferred embodiment of the process, lithium aluminum hydride is admixed with a'suitable organic solvent such as, for example, ether, the steroid'is dissolved in a non-reactive solvent such as, for example, benzene, and the admixtures then combined to form the reaction mixture. The temperature of the reaction mixture is usually maintained between about zero and about 100`degrees centigrade, with a temperature between about room temperature and the reliux temperature of the reaction mixture being preferred, for a reactionjperiod varying fromVV about one-half to about eight hours or more, with about two hours being preferred. YThe ratio of reducing agent to starting steroid may be varied considerably over a wide range, a substantial excess of the reducing agent generally being employed with mole-ratios of up to fifty to onerand above being operative. In addition to reduction of the ll-keto group, .other reducible groups when present in the molecule may be also reduced by the reducing agent, especially when Vlarge excesses of reducing agent are employed.

According to ,themethodof the present invention, a steroid 4-halo-3,20diketal havinga pregnane carbon skeleton isv reacted with an acid hydrolyzing agent to cause `selective hydrolysis of theV 20-ketal group Ywithout affecting-the 3-ketal group. In carrying out the process of the present invention, the starting steroid 4halo3,20 diketal-is mixed Ywith anv acid hydrolyzing agent. Pref- .erably the Vstarting-steroid 4-halo-3,20diketal is dissolved in an organic solvent and .this solution is admixed with at least-.the theoretical amount, and preferably an excess, of an acidhydrolyzing agent. The organic solvent may be either of the water-miscible type such as, for exampler facetonemethanol, ethanol, dioxane, and the like, or the .organic solvent may be of the water-immiscible type suchx as, for example, ether, benzene, chloroform, hexane, and the like. If a water-miscible solvent is used, the reactionl takes place in a homogeneous system, whereas, if a waterimmiscible solvent is utilized, the reaction mixture forms a two-phase heterogeneous system which must be stirred in order to bring the reactants into contact with each other and cause hydrolysis. Ordinarily, it is preferred to use a temperature between about twenty and about forty degrees centigradel in'carrying out the reaction, but temperatures as low as zeroand as highas 100 degrees centigrade or even higher areV operative. The'time required for the reaction is not critical. and may be varied between aboutone and about24 hours, the length of time being dependenton the temperature and the hydrolyzing agent employed; The amount'of hydrolyzing agent employed maybe varied over 'a wide range since the acid acts as a catalyst for the reaction. Amounts from a trace to large alyst maybe any suitable acid catalystand is preferably Aa mineral acid or Van Vorganic sulfonic acid. Representaacids, naphthalenesulfonic acid, b'enzenesulfonic acid,

iortho-chlorobenzenesulfonic acid, hydrochloric acid, and i VS lcatalysts are Vthe metaand para-toluenegulfonf- In addition to the ketalizing Ymethod described above for'preparingthe 3,20-diketal compounds employed as' startingmaterials for the lmethod of the present invention, steroid .2t-halo-l lhydroxy3,20diketals may also 3,`20diketa'l. In carrying out the reduction, a reducing 'agent is admixed with a steroid 4-halo-1l-keto 3,20-

"hydrolyzing agent forthe process of the presentinvention afstrong lacid such as, for example, sulfuric ac idp hydrochloric acid; 'metaor para-toluenesulfonic `ac1ds, naphthalenesulfonic acid, benzenesulfonic acid, ortho-chloroben'zenesulfonic acid, ,trichloroacetic acid, or the like, with sulfuric acid ,and hydrochloric acid being the preferred acids. The Aacid hydrolyzing agent is generally employed 'as 'adiluteA aqueous solution, andin dilute concentrations.

"fAcidconcentrations'in, the reactionmixture of about 0.1 "per cent to about twenty per cent are preferably employed but lower and higher concentrations are operative. Under 'thesereaction conditions the a-haloketal group is stable andremains unatected while hydrolysis of theAZO-ket'al 'takesf'placef f f l jWhen hydrolysis is substantially complete, the product 'is lisolated by conventional procedure, for example, when A mixture of 500 milligrams of 4chloro-11,17adi hydroxypregnane 3,20 dione 3,20 ethylene glycol diketal (from Preparation 3) in 25 milliliters of ether, fifteen milliliters of water, and fifteen milliliters of concentrated hydrochloric acid, was stirred at room temperature for sixteen hours. The ether phase was separated, the water phase was extracted two times with ether, and the ether extracts were combined withethe main ether phase. The combined ether solution was then concentrated to a small volume whereupon crystallization-took place. The yield of 4-ch1oro-1mAh-dihydroxypregnane- 3,20 dione 3 ethylene glycol ketal was 300 milligrams of melting point 174 to 192 degrees centgrade. Recrystallization from ethyl acetate-hexane gave 210 milligrams of purified material of melting point 194 to 196 degrees centigrade.

Following the procedure of Example 1 or 2, 4-bromoll-,l7a dihydroxypregnane 3,20 dione 3,20-ethylene glycol diketal (prepared from 4 bromo 17a hydroxypregnane 3,11,20 trione according to the procedures of Preparation 2 or 3) is hydrolyzed to give 4-bromo- 11,17a dihydroxypregnane 3,20-dione 3 ethylene glycol ketal.

Four hundred milligrams of 4 chloro 11,17adi hydroxypregnane 3,20 dione 3 ethylene glycol ketal (from Example 1) was dissolved in fifteen milliliters of chloroform and a total of 3.2 milliliters of bromine in acetic acid was added dropwise and-at such a rate as to permit decolorization of eachV drop before the subsequent drop was added. The solution was then diluted with ether, washed with a cold dilute solution of sodium bicarbonate, and with water, and dried. Removal of the i Example 5.--4 chloro 11,17ot dihydroxy 21- acetoxypregnane-3,20fdione 3-ethylene glycol ketal A mixture of 1.77 grams (0.0035 mole) of 4 chloro- 11,17a dihydroxy 2l bromopregnane 3,20 dione 3 ethyleneV glycol ketal (from Example 3), two grams of potassium acetate, fifty milligrams of potassium iodide,

and 0.5 milliliter of acetic acid in 300 milliliters of acetone was heated under redux for sixteen hours. The mixture was filteredrand the filtrate was concentrated to dryness under reduced pressure. The residue was dissolved in ethyl acetate, filtered toV remove inorganic'salts, and

' 3 ethylene glycolketal was 1.39 grams (84.8 percent);

melting point 231 to 234 degrees centigrade. Recrystallization from the same solvent raisedthe melting point to,232 to 233degrees centigrade.

AnalysisJ-'Cal'culated for C25H3'1O7Cl: C, 61.91; H, 7.69; Cl, 7.31. FoundzHC, 62.17; H, 7.73; C1, 7.16. v

i f Following the same procedure as above, other acyloxy groups may be substituted in the 21 f position byfreaction of 4 chloro 2l bromo 113,170: f dihydroxypregnane- 3,20 dione 3 ethylene glycol ketal with'the appropriate ..8 acylating agent. Suchacyloxy groups .include propionoxy, butyroyloxy, valeroyloxy, hexanoyloxy, heptanoyloxy, octanoyloxy, benzoyloxy, and others. The preferred acyloxy groups are those derived from a hydrocarbon monocarboxylic acid containing from one to eight carbon atoms, inclusive.

In addition, the corresponding 4 bromo compounds are similarly prepared from 4 bromo 11,17a dihydroxy 21 bromopregnane 3,20 dione 3 ethylene glycol ketal according to the procedure of the above example.

Example 6.-4 chloro 11,5,17.1.21-rihydroxypregnana 3,20 dione 3 ethylene glycol ketal A solution of 100 milligrams of 4 chloro 11,17a dihydroxy 21 bromopregnane 3,20 dione 3 ethylene glycol ketal (from Example 4) in fifty milliliters of alcohol and fifty milliliters of 0.1 N sodium hydroxide was permitted to stand at 25 degrees centigrade under nitrogen for ten minutes. The pH was adjusted to seven with dilute hydrochloric acid and the solution was then diluted with 200 milliliters of water and repeatedly extracted with ether. The ether extract was evaporated to dryness and the residue was purified by chromatography over Florisil to yield ten milligrams of 4 chloro 11p,17a,21 trihydroxypregnane 3,20 dione 3 ethylene glycol ketal. 'I'he structure of this compound, which was not crystalline, was confirmed by infrared analysis.

The corresponding 4 bromo compound is prepared from 4 bromo 11,17a dihydroxy 21 bromopregnane 3,20 dione 3 ethylene glycol ketal by following the procedure of the above example.

A solution of 100 milligrams of 4 chloro 17a hydroxypregnane 3,1l,20 trione 3,20 ethylene glycol diketal (from Preparation 2), four milliliters of water, and a drop of concentrated sulfuric acid, in ten milliliters of acetone was allowed to stand at room temperature for 24 hours. The solution was then diluted with water until crystallization took place. The crystalline material was isolated by filtration and was recrystallized from methylene chloride-hexane to yield purified 4 chloro- 17a hydroxypregnane 3,l1,20 trione 3 ethylene glycol ketal (87 percent); melting point 194 to 203 degrees centigrade; [MD25 plus 83 degrees (acetone).

Analyss.-Calculated for C23H33O5Cl: C, 65.00; H, 7.82; Cl, 8.34. Found: C, 65.16; H, 7.90; Cl, 8.37.

The corresponding 4-bromo compound is prepared from 4-bromo-l7a-hydroxypregnane-3,1L20-trione 3,20- ethylene glycol diketal by following the procedure of the above example.

Example 8. 4-chloro-17a-'hydroxy-2I-acetoxypregnaize- 3,11',20trione 3-ethylene glycol ketal This compound can be prepared from 4-ch1oro-17w hydroxypregnane-3,1L20-trione 3-ethylene glycol ketal of Example 6, by bromination at the 21-position according to the procedure of Example 3, followed by replacement of the bromine with an acetateV group according to the procedure of Example 4.1 The product, 4-chloro-17ahydroxy 21 acetoxypregnane3,l1,20 trione 3-ethylene glycol ketal, vis, crystallized from Visopropyl alcohol and meltsrat 228-7232 degrees centigrade.

Analysz's.-Calculated` for CzaHsiOeCl: C, 62.93; H,

Y 7.12; C1,'8.08. Found: C, 62.46; H, 7.48; Cl. 7.60.

' In the ,same manner as given in the above examples, starting from the appropriate 3,20-diketal, other steroid 4-halo-3-mono-ketals are prepared, includingA-chloropregnane-3,20dione 3-propane-1,3diol` monoketal, 4- chloropregnane,20-dione 3-octane-1,3diol monoketal, 4-chloropregnan`e-3,20-dione 3-butane-1,2diol monoketal, 4 chloro 17a hydroxypregnane 3,20-dione 3-ethylene glycol monoketal, '4-chloro-l7-hydroxypregnaue3,20

4-chloro-l1a-acetoxy-17vg4hydroXypregnane-3,20fdione 3-f tion. The mixture wasgheated at seventy degree centigrade for 0.5 hoursand was then permitted to stand at room temperature forjtvvo hours. Red needles of unsaturated hydrazone'crystallized on standing and were redissolved by the addition.of\ten,mil1i1iters of acetic acid land. ten milliliters `of chloroform. One milliliter `,of pyruvic acid was added and tlier'eaction kmixture heated '1 at fifty` degrees centigrad'e forftwo hours, after which, two

grams of sodium acetate was ajdded and the solution stirred for five minutes. After removal of the solvent under reduced pressure, the residue .was triturated three times with chloroform and filtered to remove the insoluble sodium salt of the 2,4dinitrophenylliydrazone of pyruvic arrecife This solution `vVasQaclEledf of nitrogen which was maintained throughout the reac-4 vir ` acetic anliydjridewas destroyedbythee-addition, of waterl andgtthe product Was .extracted-with methylene: dichloride; The methylene*dicliloridei solution was fvvashedfsuccese sively: with.dilute,hydrochloricacid, watergtdilite` sodium bica' biat'. slutio'ln,V Water, and--f wasf thenY d riedfover s .idium sulfatefandf 'concentratecltoV dryness@ The .fresidue Avvs Ac'rilfstallized. from .acetone andt gave,- im tvgo cropsy. 5,602 milligrams' (,7 11 percent). oli Lcrude. crystalline Gomf` pound. acetate. TheLcrude crystalline product! was re"4 crystallized, from fifty milliliters.olmethanol-after treat-` Under an@` atmosphere of nitrogen; afmixture fo'ff one`4` gram., of ltfchloro-llg'., lfl'a-dihydroxy'fZil:=acetoxypr y nanefSlO-dione 3"-.ethylene`f glycol-flc'etal,A thirty` millil-i of acetic acid, six millilitersvofjwater;arid'72 milligram o-vV serniearbazide?y hydrochloride were heated:` atse'venty degrees'V Eoentigx1adef or tivehours;v after which? tle solventi wasrcmoved bydistillationnunder reduced pressure. l Th residuewas -partiallyd-issolved innaqmixture .offwaterl fan l' ethyl acetatee giving; 49D: milligrams o :insolublemat'eri separated, lwasliefcLf rand-fevaporated fto 'dryness to'- giveeSOT milligramsoifan oil.k Both? the'solidfriraterial and'foilvveref combined and` Adissolvedfi'na* mintinefof` twenty vmillili-te of: dioxane', lve millilitersgofr Water',- tworrnilliliters was .then heated at'y SSfdegiS-ees centigradezifor ljSll-lours after. Which-the solvent--Wasf-distilled under reduced'pte sure and.- the.. resid'uei waszdissolve'dilini'methylene? dit-s chloride. After washing and drying, thelf n'i'ethy'le'ne"fJ dichl'oridesolution was-evaporate@.tofdrynessvfand tliefV liters of :pyridineg and=ytwo milliliters t0E .facetic'l anhyd The reacetylatedmaterial was worked upiasfinrEXam leg A to give 680 milligrams of crude crystalline Compound-1 y F acetate.

It is to be understood that the invention is not to be limited to the exact details -of operation oreXact cornpounds shownlanddescrib'ed, as obvious modilications and equivalents'will bepparent to one skilled in the art, and the invention is thereforevto be-limited only by the scope of the appendedqclaimsf Y We'claim: Y

1. A process for the production of a steroid 4-ha1o-3, 20-dione 3-cyclic morketal Vwhich.comprises: mixing to- 60 gether an acid hydrolyzing agentanda steroid 4-h-alo-3,

20-dione, 3,20-cyc1ic diketalhaving theflloWing basic general formula:r l Y -ll1 wherein R is selected from the class consisting of hydrogen and a lower-alkyll group, n is an integer from one to two, and X is a halogen of atomic weight from 35 to A870,Y to cause selective hydrolysis of the 20-cyclic ketal group to form a ZO-ketone group.

2. A process for the production of a 4-halopregnane-3, 20dione 3-cyclic monoketal which comprises: mixing together an acid hydrolyzing agent and a 4halopregnane3, 20-dione 3,20-cyc1ic diketal, wherein the halogen is of atomic weight from 35 to 80, at a temperature between about `zero and about 100 degrees centigrade, to cause selective hydrolysis of the 20-'cyclic lretal group to forma 20-ketone group. Y l

3. A process for the production of a4-halopregnane-3, ZO-dione 3-cyclic monoketal which comprises: mixingV together an acid hydrolyzing agent selected from the group -consisting of organic sulfonic acidsand mineral acids, and a 4halopregnane3,ZO-dione 3,20-cyclic diketal according' to claim l, at a temperature between about zero and about 100 degrees centigrade, to cause selective hydrolysis ofthe 20-cyclic ketal group to form a ZO-ketone group.

4. A process Vfor the production of a 4-halopregnane-3, ZO-dione 3-cyclic monoketal which comprises: mixing together an acid hydrolyzing agent selected from the group consisting of organic sulfonic acids and mineral acids, and a 4-halopregnane-3,ZO-dione 3,20-cyclic diketal according to claim l, inthe presence of an organic solvent, and at a temperature of about zero to about 100 degrees centigrade, to cause selective hydrolysis of the 20-cyclic ketal group to form a 20-ketone group. Y

5. A process for the production of a 4-halopregnane-3, 20-dione 3-cyclic monoketal which comprises:v mixing a mineral acid and a 4-halopregnane-3ZO-dione 3,20-cyclic diketal according to claim 1, in the presence of an organic solventfand at a temperature of about zero to about 100 degrees centigrade, to cause selective hydrolysis of the .20-cyclic ketal group to form a ZO-ketone group.

6. A process for the production of a 4-halopregnane-3, 20dion e 3-cyclic monoketal which comprises: mixing a mineral acid and a 4halopregnane3,ZO-dione 3,20-cyclic diketal according to claim l, in the presence of a waterimmiscible organic solvent, and at a temperature of about zero to about 100 degrees centigrade, to cause selective hydrolysis of Vthe 20-cyclic ketal group to form a 20- ketone group.

7. A process for the production of a 4-halopregnane- 3,20-dione 3-cyclic monoketal which comprises: mixing together a mineralk acid and a steroid 4-halo-3,20dione 3,20-cyclic diketal having the following basic general formula: Y

'Ron-0 12 together a mineral acid and a steroid 4-halo-3,20dione 3,20-cyc1ic diketal having the basic general formula:

ou LEO-Hon (CH2) n-O wherein Ris selected from the class consisting of hydro-iv gen and a lower-alkyl group, n is an integerfrom one to. two, and X is a halogen of atomic weight from 35`to 80, in the presence of an organic solvent and at a temperature between about zero and about 100degrees centi-` grade, to cause selective hydrolysis of the 20-cyc1ic ketal group torform a ZO-ketone group.

9. A process for the production of 4-halo11,17adi hydroxypregnane-3,ZO-dione 3ethylene glycol monoketal which comprises: mixing together a mineral acid and 4- halo l1,8,l7a-dihydr0xypregnane-3,20-dione 3,20-ethylene glycol diketal, wherein the halogen is of atomic weight from 35 to 80, in an organic solvent and at a temperature between about zero and about l00degrees centigrade, to cause selective hydrolysis of the 20-cyclic ketal group to form a ZO-ketone group. y Y

10. A process AforV Vthe production of 4-halo-l7a-hydroxypregnane-3,11,20-trione 3-ethyleneA glycol 'monoketal which comprises: mixing together a mineral acid andV 4 halo-1Tnt-hydroxypregnane,11,20-trione- 3,20- ethylene glycol diketal, wherein the halogen ispof atomic weight from35'to 80, in an organic solvent and at a temperature between about zero and about 100 degrees centigrade, to cause selective hydrolysis of the 20-cyclic ketal group to form a 20ketone group.

11. A proces for the production of 4-chloro11-, 17adihydroxypregnane-3,20-diene 3-ethylene glycol monoketal which comprises: mixing together a mineral acid and 4 chloro 1113,17@ dihydroxypregnane-3,ZO-dione 3,20-ethylene glycol diketal in an organic solvent .and at a temperature between about zero and about degrees centigrade, to causeselective hydrolysis of the 20- cyclic ketal group to form a 20v-ketone group. I

12. A process for the production off4-chloro-17afhyf droxypregnane-3,11,2()trione 3-ethylene glycol. monoketal which comprises: mixing together sulfuric acid and 4-chloro-17ahydroxypregnane3,11,20-trione 3,20-ethylene glycol diketal, in an organic solvent and at Ya temperature betweenabout z'er'o and about 100 degrees centgrade, to cause selective hydrolysis of the 27o-cyclic ketalV group to form a 20-ketone group.

13. A process for the production of a steroid 4-halo-V k1 l hydroxy-pregnane-3,20Jdione 3-cyclic monoketal which includes the steps of (1) mixing together 4a.V steroidV 4halo3,11,20trione having thefollowing basicf'general wherein X is a halogen of atomic weight from 35 to eighty, and a ketal-forming agent selected from the group consisting of alkane-1,2diols and alkane-1,3diols containing from two to eight carbon atoms, inclusive, in the presence of an acid catalyst to produce a steroid 4-ha1o- 3,11,20trione 3,20-alkanediol diketal, (2) reacting the thus-produced 3,20-alkanediol diketal with a reducing agent to convert the ll-ketone group to an 11o-hydroxy group, and (3) hydrolyzing the thus-produced 11hy droXy-3,20alkanediol diketal to cause selective hydrolysis of the 20-cyclic ketal group to form a 20-ketone group.

14. A process for the production of 4ch1loro-1l,17a dihydroxypregnane-3,20-dione 3-ethylene glycol ketal which includes the steps of (1) mixing together 4-chlorol7a-hydroxypregnane3,l1,20-trione and ethylene glyco1 in the presence of para-toluenesulfonic acid to produce 4-chloro-17a-hydroxypregnane-3,11,20-trione 3,20- ethylene glycol diketal, (2) reacting the thus-produced 4- chloro-17a-hydroxypregnane-3,11,20-trione 3,20-ethy1ene glycol diketal with lithium aluminum hydride, in an organic solvent which is non-reactive under the conditions of the reaction, to produce 4-chloro-1113,17a-dihydroxypregnane-3,20dione 3,20-ethylene glycol diketal, and (3) reacting the thus-produced 4chloro1l,l7a-dihydroxy pregnane-3,20dione 3,20-ethylene glycol diketal with a mineral acid, in an organic solvent, and at a temperature between about zero and about 100 degrees centgrade, to cause selective hydrolysis of the 20-cyclic ketal group to form a 20-ketone group.

15. 4 halo-11,8,17a-dihydroXypregnane-3,20-dione 3- ethylene glycol monoketals, wherein the halogen is of atomic weight from 35 to 80, which may be represented by the formula represented by the formula H O OiHa 14 17. 4 halo 17 a hydroxypregnane-3,l1,20-trione 3- ethylene glycol monoketals, wherein the halogen is of atomic weight from 35 to 80, which may be represented by the formula wherein R is an ethylene glycol ketal group and X is halogen as defined above.

18. 4 chloro 11/3,17a-dihydroxypregnane-S,20-dione 3-etl1ylene glycol monoketal.

19. 4 chloro-21 bromo-l1,3,17a-dihydroxypregnane- 3,20-dione 3-ethylene glycol monoketal.V

20. 4 chloro 17 a-hydroxypregnane-SJ1,20-trione 3- ethylene glycol monoketal.

21. A steroid 4halo3,20dione 3-cyclic monoketal having the following general formula:

l wherein X is a halogen of atomic weight from 35 to wherein R is an ethylene glycol ketal group and X 1s halogen as defined above.

eighty, R is a member of the group consisting of hydrogen and lower-alkyl, and n is an integer from one to two, and wherein the ll-position is substituted by a radical selected from the group consisting of a-hydroxy, -hydroxy and keto, and the 17-position is substituted by a member of the group consisting of hydrogen and a-hydroxy.

References Cited in the le of this patent UNITED STATES PATENTS 2,153,700 Serini Apr. 11, 1939 2,256,500 Serini Sept. 23, 1941 2,288,854 Stavely July 7, 1942 2,302,636 Koster Nov. 17, 1942 2,356,154 Fernholz Aug. 22, 1944 2,510,940 Sarett June 13, 1950 2,541,104 Sarett Feb. 13, 1951 2,541,105 Sarett Feb. 13, 1951 FOREIGN PATENTS 236,520 Switzerland 1945 OTHER REFERENCES Antonucci: I. Org. Chem., vol. 17, No. 10, received Apr. 14, 1952, pp. 1369-74. 

1. A PROCESS FOR THE PRODUCTION OF A STEROID 4-HALO-3, 20-DIONE 3-CYCLIC MONOKETAL WHICH COMPRISES: MIXING TOGETHER AN ACID HYDROLYZING AGENT AND A STEROID 4-HALO-3, 20-DIONE, 3,20-CYCLIC DIKETAL HAVING THE FOLLOWING BASIC GENERAL FORMULA: 